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PMID: 1906576 Published · ppublish English Comparative Study Journal Article

Identification of amino acid residues required for Ras p21 target activation.

Molecular and cellular biology ·Vol. 11 ·No. 8 ·1991-08-00 ·Pages 3997-4004

Marshall MS, Davis LJ, Keys RD, Mosser SD, Hill WS, Scolnick EM, Gibbs JB

Abstract

The Krev-1 gene has been shown to suppress ras-mediated transformation in vitro. Both ras and Krev-1 proteins have identical effector domains (ras residues 32 to 40), which are required for biological activity and for the interaction of Ras p21 with Ras GTPase-activating protein (GAP). In this study, five amino acid residues flanking the ras effector domain, which are not conserved with the Krev-1 protein, were shown to be required for normal protein-protein interactions and biological activity. The substitution of Krev-1 p21 residues 26, 27, 30, 31, and 45 with the corresponding amino acid residues from Ras p21 resulted in a Krev-1 protein which had ras function in both mammalian and yeast biological assays. Replacement of these residues in Ras p21 with the corresponding Krev-1 p21 amino acids resulted in ras proteins which were impaired biologically or reduced in their affinity for in vitro GAP binding. Evaluation of these mutant ras proteins have implications for Ras p21-GAP interactions in vivo.

MeSH Terms
Amino Acid Sequence Animals Cell Line DNA Replication DNA, Recombinant/metabolism GTP-Binding Proteins/genetics Genes, ras Mice Molecular Sequence Data Mutagenesis, Site-Directed Oncogene Protein p21(ras)/genetics Proto-Oncogene Proteins/genetics Proto-Oncogenes Restriction Mapping Sequence Homology, Nucleic Acid Suppression, Genetic Thymidine/metabolism Transfection rap GTP-Binding Proteins
Chemicals
DNA, Recombinant Proto-Oncogene Proteins GTP-Binding Proteins Oncogene Protein p21(ras) rap GTP-Binding Proteins Thymidine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Marshall M S
Department of Cancer Research, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486.
Davis L J
Keys R D
Mosser S D
Hill W S
Scolnick E M
Gibbs J B
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.11.8.3997-4004.1991
Published
1991-08-00
Pages
3997-4004
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC361200
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.11.8.3997-4004.1991 PMC Full Text View journal details
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